Abstract: Embodiments herein describe systems and methods to determine nucleic acid thermodynamics and uses thereof. Many embodiments utilize a sequencing chip, such as an Illumina flow cell as a high-throughput platform for performing massively parallel melt curve determination. In many embodiments, nucleic acid molecules possessing a region that forms a secondary structure are affixed to a sequencing chip and hybridized with one or more labeled oligonucleotides. As the secondary structure denatures, changes in fluorescence can be measured to determine a melt curve of specific sequences.

Abstract: Embodiments herein describe systems and methods to determine RNA structure and uses thereof. Many embodiments utilize one or more machine learning models to determine an RNA structure. In various embodiments, the machine learning model is trained using experimentally determined RNA structures. Certain embodiments identify one or more ligands or drugs that bind to an RNA structure, which can be used to treat an individual for a disease, disorder, or infection. Various embodiments determine structure of other molecules, including DNA, proteins, small molecules, etc. Further embodiments determine interactions between multiple molecules and/or molecule types (e.g., RNA-RNA interactions, RNA-DNA interactions, DNA-protein interactions, etc.

Abstract: Embodiments herein describe systems and methods to enhance RNA stability and uses thereof. Many embodiments alter the sequence of an RNA therapeutic molecule (e.g., vaccines) to encode for a variant peptide while maintaining and/or increasing stability of the RNA therapeutic.

Abstract: Embodiments herein describe systems and methods to enhance RNA stability and uses thereof. Many embodiments alter the sequence of an RNA therapeutic molecule (e.g., vaccines) to encode for a variant peptide while maintaining and/or increasing stability of the RNA therapeutic.

Abstract: Systems and methods for generating RNA nanostructures capable of linking RNA structures and capable of securing aptamers in an active and stable structure are disclosed. Generally, RNA possesses many structural properties to create novel nanostructures and machines. RNA tertiary structure is composed of discrete and recurring components known as tertiary ‘motifs’. Along with the helices that they interconnect, many of these structural motifs appear highly modular. Systems and methods herein generate a motif library including canonical and noncanonical motifs to design a candidate path to connect one or more RNA molecules. These paths can also be used to secure RNA aptamers to improve aptamer stability and activity.

Abstract: Systems and methods for isothermal amplification of nucleic acids in a ratiometric manner are disclosed. Methods of isothermal amplification of nucleic acids are convenient for areas that lack reliable electricity and/or funding for precision lab equipment. However, these methods typically result in non-ratiometric amplification of target sequences, thus preventing quantitative analysis or application of the results, such as for diagnostic testing. Systems and methods herein provide a method of isothermal amplification that ratiometrically amplifies target sequences, thus expanding the reach of diagnostics into remote and/or economically disadvantaged areas.

Abstract: Systems and methods for assessing mRNA in vivo and/or in vitro stability are disclosed. Some embodiments methods obtain RNA indexed or barcoded RNA molecules which are then tested against various conditions including stability inside of cells, stability in cell lysate, and stability in solution (e.g., for storage and/or transportation). Additional embodiments describe methods to determine degradation points with single base resolution.

Abstract: Embodiments herein describe systems and methods to enhance RNA translation and stability and uses thereof. Many embodiments generate RNA molecules possessing increased structure and/or reduced free energy over an initial sequence. Such RNA molecules can be used as therapeutics and/or vaccines.